Chapple Sarah J, Cheng Xinghua, Mann Giovanni E
Cardiovascular Division, British Heart Foundation Centre of Research Excellence, School of Medicine, King's College London, 150 Stamford Street, London SE1 9NH, U.K.
Redox Biol. 2013 May 23;1(1):319-31. doi: 10.1016/j.redox.2013.04.001.
4-hydroxynonenal (HNE) is a lipid hydroperoxide end product formed from the oxidation of n-6 polyunsaturated fatty acids. The relative abundance of HNE within the vasculature is dependent not only on the rate of lipid peroxidation and HNE synthesis but also on the removal of HNE adducts by phase II metabolic pathways such as glutathione-S-transferases. Depending on its relative concentration, HNE can induce a range of hormetic effects in vascular endothelial and smooth muscle cells, including kinase activation, proliferation, induction of phase II enzymes and in high doses inactivation of enzymatic processes and apoptosis. HNE also plays an important role in the pathogenesis of vascular diseases such as atherosclerosis, diabetes, neurodegenerative disorders and in utero diseases such as pre-eclampsia. This review examines the known production, metabolism and consequences of HNE synthesis within vascular endothelial and smooth muscle cells, highlighting alterations in mitochondrial and endoplasmic reticulum function and their association with various vascular pathologies.
4-羟基壬烯醛（HNE）是由n-6多不饱和脂肪酸氧化形成的脂质氢过氧化物终产物。血管系统中HNE的相对丰度不仅取决于脂质过氧化和HNE合成的速率，还取决于通过谷胱甘肽-S-转移酶等II相代谢途径对HNE加合物的清除。根据其相对浓度，HNE可在血管内皮细胞和平滑肌细胞中诱导一系列应激效应，包括激酶激活、增殖、II相酶的诱导，以及高剂量时酶促过程的失活和细胞凋亡。HNE在动脉粥样硬化、糖尿病、神经退行性疾病等血管疾病以及子痫前期等子宫内疾病的发病机制中也起着重要作用。本文综述了血管内皮细胞和平滑肌细胞内HNE合成的已知产生、代谢及后果，强调了线粒体和内质网功能的改变及其与各种血管病变的关联。
